Dichloromethane → HCID 22769937, compound

Cyclohexylhydrazine hydrochloride (AK Scientific) (700 g, 4643 mmol) was added to a stirred solution of DCM (3000 mL) and ice cold 2M sodium hydroxide solution (1778 mL, 3556 mmol). The reaction mixture was stirred for 10 minutes at room temperature. The resulting phases were separated and the aqueous layer was extracted with DCM (4×2000 mL). The combined organic extracts were dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The resulting solid was dissolved in water (1300 mL), to which acetic acid (1300 mL) and ethyl acetoacetate (Fluka) (450 mL, 3556 mmol) were added and the reaction mixture was stirred at 85° C. for 1 hour. The resulting mixture was concentrated to dryness under reduced pressure and the residue was dissolved in DCM (3000 mL) and water (1000 mL). The pH was adjusted to pH 9 using 2M K2CO3 (aq), the phases were separated and the organic extract was washed with brine (1×2 L). The first aqueous layer was saturated with sodium chloride and the combined aqueous phases were extracted with DCM (4×2 L). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield a solid. The crude solid was pulverized, TBME (2000 mL) was added and the mixture was stirred at 50° C. for 1 hour, followed by 1 hour at room temperature. The resulting suspension was filtered, washing the solid with TBME (4×500 mL). The isolated solid was dried under vacuum at 45° C. for 16 hours to afford the title compound;

1. customThe resulting phases were separated
2. extractionthe aqueous layer was extracted with DCM (4×2000 mL)
3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. additionwere added
7. stirringthe reaction mixture was stirred at 85° C. for 1 hour
8. concentrationThe resulting mixture was concentrated to dryness under reduced pressure
9. dissolutionthe residue was dissolved in DCM (3000 mL)
10. customthe phases were separated
11. extractionthe organic extract
12. washwas washed with brine (1×2 L)
13. extractionthe combined aqueous phases were extracted with DCM (4×2 L)
14. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated under reduced pressure
17. customto yield a solid
18. stirringthe mixture was stirred at 50° C. for 1 hour
19. waitfollowed by 1 hour at room temperature
20. filtrationThe resulting suspension was filtered
21. washwashing the solid with TBME (4×500 mL)
22. customThe isolated solid was dried under vacuum at 45° C. for 16 hours

ORD record

ord-8f00a0cf7f364435a027a4577f4f3249

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403810B2